Cannabinoid pouch

ABSTRACT

A pouch designed for administration of an active ingredient in the oral cavity is disclosed, the pouch containing a matrix composition having a combination of an amount of one or more cannabinoids and a water-insoluble composition. Also, pouches for use as a medicament, for use in alleviation of pain, and for use in mitigation of appetite deficiency are disclosed. Further, a method of alleviation of pain and a method of mitigation of appetite deficiency using the pouch are disclosed.

FIELD OF INVENTION

The invention relates to pouches comprising cannabinoids.

BACKGROUND OF THE INVENTION

Cannabinoids or derivatives thereof have been used for medical purposes.

Cannabis is often administering by smoking. A problem related to suchadministration is that the rapid absorption into the blood via the lungmay be undesirable. Not only may the smoking as such have side effects,but the administration may be difficult to manage.

SUMMARY OF THE INVENTION

The invention relates to a pouch designed for administration of anactive ingredient in the oral cavity,

the pouch containing a matrix composition comprising a combination of anamount of one or more cannabinoids and a water-insoluble composition.

According to the invention, the matrix composition in the pouchcomprises one or more cannabinoids as the active ingredient. The pouchalso comprises a membrane or barrier defining an inner space sealed bythe membrane. This membrane or barrier is water-permeable, so that, whenin use, the saliva enters the inner space through the membrane orbarrier, where the one or more cannabinoids are dissolved or otherwisemobilized by the saliva. Then, the saliva and the mobilized or dissolvedcannabinoid(s) may cross the membrane again thereby releasing the one ormore cannabinoids and the optional other substances to the oral cavity.

On the other hand, the water-insoluble composition may be retainedinside the pouch even during use due to a combination of itswater-insoluble characteristics and e.g. a larger dimension of thewater-insoluble composition, for examples as a powder composition,compared to the openings of the membrane. In other words, a pouch with amatrix composition may be provided that, during use, release said one ormore cannabinoids while retaining the water-insoluble composition. Inthis way, according to an embodiment, the water-insoluble compositionmay be affect the release of said one or more cannabinoids in a mannerso as to achieve a prolonged release, allowing the user to feel theeffect of the released cannabinoids and thus control the release totaldose of cannabinoids by removing and optionally re-inserting the pouchin order to achieve the desired effect.

One challenge with respect to dosing of cannabinoids is that the desiredeffect on a particular individual depends on several factors apart ofthe dose itself, for example the body weight of the individual and otherfactors affecting the how a certain dose translates into a specificplasma concentration, but also the efficiency of the cannabinoids whichmay be lowered after prolonged use and differ from person to person.Finally, the symptoms experienced by a specific user may also differfrom time to time and thus a suitable dose one day may be too high ortoo low the next day. Consequently, it is desirable that a person canself-adjust the dose according to the individual circumstances of thespecific situation. However, one challenge here may be that pre-meteredstandard doses may not necessarily fit the needs of the individual user,whereas more customized doses are expensive in distribution andinconvenient in handling. Finally, due to the delay of the effectexperienced by the user after administration of one pouch to the oralcavity may cause the user to insert a second pouch in the oral cavity,after which the experienced effect becomes higher than intended.

The present invention provides a pouch system for efficient and fastrelease of cannabinoids circumventing the metabolic system and allowingthe user to adjust the dose to the specific need, by allowing the doseof cannabinoids released to be adjusted by the usage time. Other systemsmay rely on single dose administrations, such as ingestible pills, fastdissolving delivery platforms etc. The present invention, however,provides a much more flexible delivery vehicle while avoiding thedisadvantages associated with e.g. smoking marijuana, as e.g. inhalationof carcinogenic substances.

Critical for the invention is the combined presence in the matrixcomposition of both the one or more cannabinoids and also thewater-insoluble composition. The insoluble composition may preferablywork to delay the release of said one or more cannabinoids for examplein the sense that the one or more cannabinoids are bound to thewater-insoluble composition so as to act as a carrier, or by controllingthe release of the one or more cannabinoids by, during use, controllingthe access of water or saliva to the one or more cannabinoids.

One important aspect of the invention is that both the one or morecannabinoids and the water-insoluble composition must be present in thepouch. The combination of the cannabinoids and the water-insolublecomposition allows the cannabinoids to be released, advantageously underinfluence of the water-insoluble composition. The water-insolublecomposition may therefore act as a carrier or be part of a carrier, e.g.by the cannabinoids being bound or adhered to the carrier.Alternatively, the cannabinoids may be distributed between thewater-insoluble composition, i.e. interspersed between thewater-insoluble composition, such that the water-insoluble compositionforms a matrix or forms part of a matrix for the one or morecannabinoids. Thus, the carrier may function by influencing the releaseof the cannabinoids and/or by stabilizing the cannabinoids beforerelease.

According to an embodiment of the invention, the pouch comprise afurther active ingredient other than said one or more cannabinoids.

According to an embodiment of the invention, the pouch consists of saidmatrix composition and a sealed barrier enclosing said matrixcomposition.

According to an advantageous embodiment of the invention the matrixcomposition comprises said water-insoluble composition in an amount ofbetween 1 and 80 percent weight of said matrix composition.

According to an embodiment of the invention, the matrix compositioncomprises said water-insoluble composition in an amount of between 2 and70 percent weight of said matrix composition.

According to an embodiment of the invention, the matrix compositioncomprises said water-insoluble composition in an amount of between 3 and60 percent weight of said matrix composition.

According to an embodiment of the invention, the matrix compositioncomprises said water-insoluble composition in an amount of between 5 and50 percent weight of said matrix composition.

According to an advantageous embodiment of the invention thewater-insoluble composition comprises a water-insoluble carrier.

One advantage of the above embodiment may be that a user controlledrelease of said one or more cannabinoids may be provided by means ofsaid pouched product. This may facilitate a more individualized dosageof cannabinoids, by allowing each user to individually adjust therelease dosage e.g. in view of the instantaneously experienced effectand/or previous experience. Also, by providing a relatively slow releaseof said cannabinoids, e.g. in combination with a relatively high totalcontent of cannabinoids, an advantageous and individualized usercontrolled release of cannabinoids may be obtained.

A further advantage may be that a relatively effective and/or fastuptake of cannabinoids may be provided, due to a local highconcentration around the pouch, thereby giving a relatively steepconcentration gradient across the mucous membrane.

According to an embodiment of the invention, the water-insolublecomposition is a water-insoluble carrier.

One advantage of the above embodiment may be that a relativelylong-lasting release of said one or more cannabinoids may be obtained.By utilizing the water-insoluble carrier as a release prolongingmeasure, a slow release may be obtained, which for example allows theuser to gradually feel the effect of the released cannabinoids andremove the pouch from the oral cavity when the desired effect has beenobtained. Also, a slow release may allow the total amount of said one ormore cannabinoids to be relatively high, without giving a too highrelease per time even at initiation of the use. For example, the totalamount of said one or more cannabinoids may be adapted to cover morethan one usage events, thereby allowing the user to remove and reinsertthe pouch into the oral cavity as preferred.

According to an advantageous embodiment of the invention thewater-insoluble composition comprises cellulose.

One advantage of the above embodiment may be that the water-insolublecomposition comprises cellulose being both suitable as a carrier for theone or more cannabinoids and as a humectant.

According to an advantageous embodiment of the invention the celluloseis present in an amount of 5 to 60 percent of said matrix composition.

According to an embodiment of the invention the cellulose is present inan amount of 10 to 60 percent of said matrix composition.

According to an advantageous embodiment of the invention thewater-insoluble composition comprises microcrystalline cellulose (MCC).

One advantage of the above embodiment may be that the water-insolublecomposition comprises MCC being both suitable as a carrier for the oneor more cannabinoids and as a humectant.

According to an advantageous embodiment of the invention the MCC ispresent in an amount of 5 to 60 percent of said matrix composition.

In an embodiment of the invention said cellulose is selected from thelist consisting of microcrystalline cellulose (MCC);carboxymethylcellulose (CMC), such as sodium carboxymethylcellulose;hydroxypropyl methylcellulose (HPMC); methylcellulose; ethylcellulose(EC); methylethylcellulose (MEC); hydroxyethyl cellulose (HEC);hydroxyethyl methylcellulose (HEMC); and any combination thereof.

According to an embodiment of the invention the cellulose, such asmicrocrystalline cellulose forms a carrier, or part of.

According to an advantageous embodiment of the invention thewater-insoluble composition comprises an ion-exchange resin.

One advantage of the above embodiment may be that a relatively highstability of said one or more cannabinoids may be obtained, e.g.comparing with not having any carrier.

According to an advantageous embodiment of the invention theion-exchange resin is present in an amount of 5 to 60 percent of saidmatrix composition.

According to an embodiment of the invention the ion-exchange resin ispresent in an amount of 10 to 60 percent of said matrix composition.

According to an embodiment of the invention the ion-exchange resin is acarrier, or part thereof.

According to an advantageous embodiment of the invention theion-exchange resin is a basic ion-exchange resin.

According to an embodiment of the invention the basic ion-exchange resinis a carrier, or part thereof.

According to an embodiment of the invention the basic ion-exchange resinis a strongly basic ion-exchange resin.

According to an embodiment of the invention the strongly basicion-exchange resin is a carrier, or part thereof.

According to an embodiment of the invention, when using the basicion-exchange resin, particularly when using a strongly basicion-exchange resin, a pH-controlling agent, preferably an acidicpH-controlling agent or buffering agent, is added to the matrixcomposition. Thereby, an advantageous release of said one or morecannabinoids from the ion-exchange resin may be obtained by facilitatingrelease from the basin ion-exchange resin.

According to an advantageous embodiment of the invention the matrixcomposition further comprises a water-soluble composition.

According to an advantageous embodiment of the invention thewater-soluble composition comprises sugar alcohol.

According to an embodiment of the invention, said sugar alcohol may be asingle type of sugar alcohol, or a mixture of two or more sugaralcohols.

According to an embodiment of the invention the water-solublecomposition is sugar alcohol.

According to an advantageous embodiment of the invention said matrixcomposition comprises said sugar alcohol in an amount of 1 to 90 percentby weight of said matrix composition.

According to an embodiment of the invention said sugar alcohol in anamount of 5 to 80 percent by weight of said matrix composition.

Thus, according to one or more of the above embodiments, the matrixcomposition comprises the water-insoluble composition in combinationwith one or more further substances, such as a water-solublecomposition, such as sugar alcohol.

According to an embodiment of the invention the water-solublecomposition comprises sugar.

According to an embodiment of the invention said matrix compositioncomprises said sugar in an amount of 1 to 90 percent by weight of saidmatrix composition

According to an embodiment of the invention, the water-solublecomposition comprises a combination of sugar and sugar alcohol.

In some embodiments, the water-insoluble composition comprises acarrier, or forms a carrier.

According to an advantageous embodiment of the invention the matrixcomposition comprises a pH controlling agent.

An advantage of the above embodiment may be that the cannabinoids arereleased more effectively from the pouch. This may be especially whenthe matrix composition comprises an ion exchange resin as a carrier forthe one or more cannabinoids.

For example, the pH controlling agent may comprise or be a bufferingagent, which is acidic, i.e. adapted to ensure a relatively low pH valuein the oral cavity below 7 so as to ensure release of said one or morecannabinoids from an ion exchange resin. In the matrix composition, suchpH controlling agents may be kept inactive by separating it from thecomplex between the one or more cannabinoids and the ion-exchange resinuntil activated by water from the saliva during use.

According to an advantageous embodiment of the invention the pHcontrolling agent is an acidic pH controlling agent and/or a basic pHcontrolling agent.

According to an advantageous embodiment of the invention the matrixcomposition further comprises a release controlling composition.

In an embodiment of the invention, the release controlling compositionis provided as a powder composition having an average particle below theaverage particle size of the remaining matrix composition. E.g. theaverage particle size of the release controlling composition may be lessthan half of the average particle size of the remaining matrixcomposition. Especially in embodiments, where the matrix compositioncomprises a water-soluble composition, such as sugar alcohols, theaverage particle size of the release controlling composition mayadvantageously be smaller than the average particle size of thewater-soluble composition, such as the sugar alcohols. Thereby, therelease controlling composition may advantageously control the releaseof the water-soluble composition, if any, and/or the cannabinoids, e.g.by controlling the moistening of the pouch, i.e. the supply of saliva tothe matrix composition.

According to an advantageous embodiment of the invention the releasecontrolling composition is hydrophobic.

One advantage of the above embodiment may be that an effective controlof the supply of water in the form of saliva may be obtained, thusgiving control of the release.

According to an advantageous embodiment of the invention said releasecontrolling composition comprises one or more metallic stearates.

According to an advantageous embodiment of the invention said releasecontrolling composition comprises magnesium stearate.

According to an embodiment of the invention said release controllingcomposition comprises magnesium stearate.

According to an advantageous embodiment of the invention said releasecontrolling composition comprises calcium stearate.

According to an advantageous embodiment of the invention the matrixcomposition comprises said release controlling composition in an amountof between 1 and 20 percent by weight of said matrix composition.

According to an embodiment of the invention the matrix compositioncomprises said release controlling composition in an amount of between 3and 15 percent by weight of said matrix composition.

According to an embodiment of the invention the matrix compositioncomprises magnesium stearate as said release controlling composition inan amount of between 3 and 15 percent by weight of said matrixcomposition.

According to an advantageous embodiment of the invention the matrixcomposition is a powdered matrix composition.

According to an embodiment of the invention the water-insolublecomposition is a powder composition.

For example, when the water-insoluble composition is a water-insolublecarrier, it may be provided as a powder composition.

According to an advantageous embodiment of the invention powdered matrixcomposition has an average particle size of below 1200 micrometer.

According to an advantageous embodiment of the invention powdered matrixcomposition has an average particle size of above 1 micrometer.

According to an embodiment of the invention, the powdered matrixcomposition as an average particle size is between 1 and 1200micrometer.

In an embodiment of the invention the powdered matrix composition has anaverage particle size of said powdered composition is between 1 and 400micrometer.

According to an embodiment of the invention, the average powder size islarger than the average opening dimension of the pouch.

According to an embodiment of the invention the characteristic openingdimension is adapted to the characteristic dimension of the matrixcomposition so as to retain the matrix composition inside the pouchbefore use and/or to retain the insoluble composition inside the pouchduring use.

According to an advantageous embodiment of the invention the pouchcomprises a water-permeable membrane, comprising e.g. woven or non-wowenfabric.

According to an advantageous embodiment of the invention the one or morecannabinoids are on crystalline form.

According to an embodiment of the invention, the one or morecannabinoids comprises cannabidiol or consists of cannabidiol oncrystalline form.

According to an advantageous embodiment of the invention the one or morecannabinoids are physically or chemically bound to at least a part ofthe matrix composition acting as a carrier.

According to an advantageous embodiment of the invention the one or morecannabinoids have been granulated with the carrier.

According to an advantageous embodiment of the invention the matrixcomposition comprises said one or more cannabinoids in an amount ofbetween 0.1 and 50 percent weight of said matrix composition.

In embodiments, where a cannabinoid extract is used as a source of saidone or more cannabinoids, the matrix composition may in some casescomprise a lower amount of cannabinoids, such as e.g. 0.1 to 30 percentby weight of the matrix composition, especially when a relativelydiluted extract is used, i.e. where the content of cannabinoids isrelatively low.

According to an advantageous embodiment of the invention the matrixcomposition comprises said one or more cannabinoids in an amount of 0.25to 500 milligrams.

According to an advantageous embodiment of the invention said one ormore cannabinoids are derived from cannabis.

In an alternative embodiment, the composition may comprise one or morecannabinoids, where one or all of the cannabinoids are not derived fromcannabis and e.g. comprise synthetic cannabinoids.

According to an advantageous embodiment of the invention said one ormore cannabinoids comprises at least two cannabinoids.

According to an advantageous embodiment of the invention said one ormore cannabinoids consists of two cannabinoids.

Thus, according to the above embodiment, the matrix composition and thepouch is substantially free of further cannabinoids other than said twocannabinoids. Moreover, it should be understood according to the aboveembodiment that the pouch comprises a combination of two cannabinoids,i.e. a combination of two different types of cannabinoids. Further, thepouch according to the above embodiment comprises only two cannabinoids.In practical scenarios, it may not be easy to achieve completeelimination of certain substances, thus, there may in some embodimentsbe small or trace amounts of further cannabinoids, e.g. due to a smalldegree of degradation of the intended cannabinoid(s).

According to an advantageous embodiment of the invention said one ormore cannabinoids consists of one cannabinoid, such astetrahydrocannabinol or cannabidiol.

According to an advantageous embodiment of the invention the one or morecannabinoids comprise cannabidiol.

According to an advantageous embodiment of the invention said one ormore cannabinoids comprises cannabidiol in an amount of between 10 and100 percent by weight of the one or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisescannabidiol in an amount of between 20 and 100 percent by weight of theone or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisescannabidiol in an amount of between 30 and 90 percent by weight of theone or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisescannabidiol in an amount of between 50 and 90 percent by weight of theone or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisescannabidiol in an amount of between 70 and 99 percent by weight of theone or more cannabinoids.

In one embodiment, the one or ore cannabinoids consists essentially ofcannabidiol.

According to an advantageous embodiment of the invention the one or morecannabinoids comprise tetrahydrocannabinol.

According to an advantageous embodiment of the invention the one or morecannabinoids comprises tetrahydrocannabinol in an amount of between 10and 100 percent by weight of the one or more.

In an embodiment of the invention the one or more cannabinoids comprisestetrahydrocannabinol in an amount of between 20 and 100 percent byweight of the one or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisestetrahydrocannabinol in an amount of between 30 and 90 percent by weightof the one or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisestetrahydrocannabinol in an amount of between 50 and 90 percent by weightof the one or more cannabinoids.

In an embodiment of the invention the one or more cannabinoids comprisestetrahydrocannabinol in an amount of between 70 and 99 percent by weightof the one or more cannabinoids.

In one embodiment, the one or more cannabinoids consists essentially oftetrahydrocannabinol.

According to an advantageous embodiment of the invention the pouchcomprises a humectant.

In one embodiment the humectant may be the water-insoluble compositionor be part of the water-insoluble composition, whereas in otherembodiments it may be provided as a separate composition in the pouch.When the water-insoluble composition comprises a carrier or is part of acarrier, the humectant may be provided as the water-insoluble carrier oras a separate composition in the pouch.

Suitable humectants may include one or more hygroscopic materials, suchas cellulose, sugar alcohols, and other hygroscopic materials.

According to an advantageous embodiment of the invention the humectantcomprises one or more from the list consisting of sugar alcohol,alginate, cellulose, such as microcrystalline cellulose, pectin, xanthangum.

The humectant may in one embodiment be provided separately from thewater-insoluble composition.

The humectant may in one embodiment be provided by the water-insolublecomposition, i.e. the water-insoluble composition is a humectant orcomprises a humectant. When the water-insoluble composition comprises acarrier, or is part of a carrier, the carrier may be a humectant.

The invention further relates to the pouch according to the invention orany of its embodiments for use as a medicament.

The invention further relates to the pouch according to the invention orany of its embodiments for use in alleviation of pain.

According to an advantageous embodiment of the invention said pain isneurotic pain.

According to an advantageous embodiment of the invention said pain iscancer-related pain.

The invention further relates to the pouch according to the invention orany of its embodiments for use in mitigation of appetite deficiency.

The invention further relates to a method of alleviation of pain, suchas neurotic pain or cancer-related pain, by administering an effectiveamount of said one or more cannabinoids by means of the pouch accordingto the invention or any of its embodiments.

The invention further relates to a method of mitigation of appetitedeficiency by administering an effective amount of said one or morecannabinoids by means of the pouch according to the invention or any ofits embodiments.

DETAILED DESCRIPTION OF THE INVENTION

Definitions

As used herein the term “pouch” is intended to mean a containertypically formed by a web of a fibrous material enclosing a cavity. Thepouch is pouch designed for administration of an active ingredient inthe oral cavity, and thus it is adapted for oral use, it is non-toxicand not water-soluble. The fibrous material may e.g. form a woven ornon-woven web or fabric. The pouch may for example be sealed by bondingtwo corresponding pieces of web or fabric to each other along theiredges to form a cavity for the one or more cannabinoids and thewater-insoluble composition. In order to release the one or morecannabinoids, the pouch is made water-permeable so as to allow salivafrom the oral cavity to penetrate the pouch and enter the cavity, wherethe saliva can come into contact with the one or more cannabinoids,whereby the one or more cannabinoids are released from the oral pouch.

As used herein the term “carrier” is intended to mean a substance thatbinds, physically or chemically an active ingredient. Unless otherwisestated, the term “carrier” refers to a carrier for said one or morecannabinoids. Examples of carriers include ion exchange resins, andcellulose, e.g. microcrystalline cellulose. The one or more cannabinoidsmay for example be granulated with the cellulose, when using celluloseas the water-insoluble composition. When using ion-exchange resin as thewater-insoluble composition, the one or more cannabinoids are bound tothe ion-exchange resin.

As used herein the term “cannabinoids” refers to cannabinoids derivedfrom cannabis plants and synthetic cannabinoids. Examples ofcannabinoids include cannabidiol, tetrahydrocannabinol, cannabinol, etc.

As used herein the terms “cannabidiol” and “CBD” both refer toCannabidiol (IUPAC:2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol).

As used herein the terms “tetrahydrocannabinol” and “THC” both refer toTetrahydrocannabinol, (−)-trans-Δ⁹-tetrahydrocannabinol (IUPAC:(−)-(6aR,10aR)-6,6,9-Trimethyl-3-pentyl-6a,7,8,10a-tetrahydro-6H-benzo[c]chromen-1-ol).

As used herein the term “powder composition” refers to composition inthe form of powder, i.e. as a particulate material having a relativelysmall average particle size, for example between 1 and 1200 micrometer.

As used herein the term “humectant” is understood as a moistening agentused to attract moisture or water in the form of saliva. Humectants maytypically include suitably hygroscopic compositions. In some cases,humectants may also be described as moistening agents, due to their rolein attraction of moisture. Examples of humectants include cellulose,such as microcrystalline cellulose and other cellulose types disclosedherein, sugar alcohols, such as those disclosed herein, alginate,cellulose, such as microcrystalline cellulose, pectin, xanthan gum, etc.

As used herein the term “water-insoluble composition” refers to acomposition having a relatively low water-solubility, for exampleconsisting of water-soluble substances having a water-solubility of lessthan 1 gram of water-insoluble composition per 100 mL of water measuredat 25 degrees Celsius and pH of 7.0. When referring to an “insoluble”composition or substance, water-insoluble is meant, unless otherwisestated. Likewise, when referring to “soluble”, water-soluble is meantunless otherwise stated. The water-insoluble composition is part of thematrix composition. In some embodiments, water-soluble composition ispart of a carrier or forms such carrier.

As used herein the term “matrix composition” is used as reference to thetotal content of the pouch, i.e. the entire composition enclosed by thepouch. Typically, it therefore corresponds to the pouch excluding theouter membrane of the pouch.

Typically, the pouches comprise openings, where the characteristicopening dimension is adapted to a characteristic dimension of the matrixcomposition so as to retain the matrix composition inside the pouchbefore use and/or to retain a part of the matrix composition, such as aninsoluble composition, inside the pouch during use.

In order to obtain a pouch having suitable opening dimensions in view ofthe matrix composition to be used, the material for the pouch may beselected accordingly, e.g. comprising e.g. wowen or non-wowen fabric.

In other words, according to the various embodiments, the pouch forms amembrane allowing passage of saliva and prevents or inhibits passage ofsaid water-insoluble composition. The membrane of the pouch may be ofany suitable material e.g. wowen or non-wowen fabric (e.g. cotton,fleece etc.), heat sealable non-wowen cellulose or other polymericmaterials such as a synthetic, semi-synthetic or natural polymericmaterial. An example of suitable pouch material is paper made of pulpand a small amount of wet strength agent. A material suitable for usemust provide a semi-permeable membrane layer to prevent the powder orcomposition from leaving the bag or pouch during use. Suitable materialsare also those that do not have a significant impact on the release ofcannabinoids from the pouch.

The powder is filled into pouches and is maintained in the pouch by asealing. An ideal pouch is chemically and physically stable, it ispharmaceutically acceptable, it is insoluble in water, it is easy tofill with powder and seal, and it provides a semi-permeable membranelayer which prevent the powder from leaving the bag, but permit salivaand therein dissolved or sufficiently small suspended components fromthe powder in the pouch, such as cannabinoids, to pass through saidpouch.

The pouch may be placed in the oral cavity by the user. Saliva thenenters into the pouch, and the one or more cannabinoids and othercomponents, which are soluble in saliva, start to dissolve and aretransported with the saliva out of the pouch into the oral cavity, wherethe cannabinoid may be absorbed.

According to an embodiment of the invention, the matrix composition mayfurther comprise one or more enhancers.

In an embodiment of the invention, said enhancers are selected from thegroup consisting of bile salts, cetomacrogols, chelating agents,citrates, cyclodextrins, detergents, enamine derivatives, fatty acids,labrasol, lecithins, phospholipids, syntetic and natural surfactants,nonionic surfactants, cell envelope disordering compounds, solvents,steroidal detergents, chelators, solubilization agents, charge modifyingagents, pH control agents, degradative enzyme inhibitors, mucolytic ormucus clearing agents, membrane penetration-enhancing agents, modulatoryagents of epithelial junction physiology, vasodilator agents, selectivetransport-enhancing agents, or any combination thereof. pH controlagents include buffers.

In an embodiment of the invention, said enhancers are selected from thegroup consisting of cetylpyridinium chloride (CPC), benzalkoniumchloride, sodium lauryl sulfate, polysorbate 80, Polysorbate 20,cetyltrimethylammonium bromide, laureth 9, sodium salicylate, sodiumEDTA, EDTA, aprotinin, sodium taurocholate, saponins, bile saltderivatives, fatty acids, sucrose esters, azone emulsion, dextransulphate, linoleic acid, labrafil, transcutol, urea, azone, nonionicsurfactants, sulfoxides, sauric acid/PG, POE 23 lauryl ether,methoxysalicylate, dextran sulfate, methanol, ethanol, sodium cholate,Sodium taurocholate, Lysophosphatidyl choline, Alkylglycosides,polysorbates, Sorbitan esters, Poloxamer block copolymers, PEG-35 castoroil, PEG-40 hydrogenated castor oil, Caprocaproyl macrogol-8 glycerides,PEG-8 caprylic/capric, glycerides, Dioctyl sulfosuccinate, Polyethylenelauryl ether, Ethoxydiglycol, Propylene glycol, mono-di-caprylate,Glycerol monocaprylate, Glyceryl fatty acids (C.sub.8-C.sub.18)ethoxylated Oleic acid, Linoleic acid, Glyceryl caprylate/caprate,Glyceryl monooleate, Glyceryl monolaurate, Capryliccapric triglycerides,Ethoxylated nonylphenols, PEG-(8-50) stearates, Olive oil PEG-6, esters,Triolein PEG-6 esters, Lecithin, d-alpha tocopherol polyethylene glycol1,000 succinate, Citric acid, Sodium citrate, BRIJ, Sodium laurate,5-methoxysalicylic acid, Bile salts, Acetyl salicylate, ZOT,Docosahexaenoic acid, Alkylglycosides, Sodium glycocholate (GC-Na),Sodium taurocholate (TC-Na), EDTA, Choline salicylate, Sodium caprate(Cap-Na), N-lauryl-beta-D-maltopyranoside (LM), Diethyl maleate,Labrasol, Sodium salicylate, Mentol, Alkali metal alkyl sulphate, Sodiumlauryl sulphate, Glycerin, Bile acid, Lecithin, phosphatidylcholine,phosphatidylserine, sphingomyelin, phophatidylethanolamine, cephalin,lysolecithin, Hyaluronic acid: alkalimetal salts, sodium, alkaline earthand aluminum, Octylphenoxypolyethoxyethanol, Glycolic acid, Lactic acid,Chamomile extract, Cucumber extract, Borage oil, Evening primrose oil,Polyglycerin, Lysine, Polylysine, Triolein, Monoolein, Monooleates,Monolaurates, Polydocanol alkyl ethers, Chenodeoxycholate, Deoxycholate,Glycocholic acid, Taurocholic acid, Glycodeoxycholic acid,Taurodeoxycholic acid, Sodium glycocholate, Phosphatidylcholine,Phosphatidylserine, Sphingomyelin, Phosphatidylethanolamine, Cephalin,Lysolecithin, Alkali metal hyaluronates, Chitosan, Poly-L-arginine,Alkyl glucoside, Saccharide alkyl ester, Fusidic acid derivatives,Sodium taurdihydrofusidate (STDHF), L-α-phosphatidylcholine Didecanoyl(DDPC), Nitroglycerine, nitropruside, NOC5[3-(2-hydroxy-l-(methyl-ethyl)-2-nitrosohydrazino)-l-propanamine], NOC12[iV-ethyl-2-(l-ethyl-hydroxy-2-nitrosohydrazino)-ethanamine, SNAP[S-nitroso-N-acetyl-DL-penicillamine, NORI, NOR4, deacylmethylsulfoxide, azone, salicylamide, glyceryl-l,3-diacetoacetate,l,2-isopropylideneglycerine-3-acetoacetate), Amino acids, Amino acidsalts, monoaminocarboxlic acids, Glycine, alanine, phenylalanine,proline, hydroxyproline, hydroxyamino acids, serine, acidic amino acids,aspartic acid, Glutamic acid, Basic amino acids, Lysine, N-acetylaminoacids, N-acetylalanine, N-acetylphenylalanine, TM-acetylserine,N-acetylglycine, N-acetyllysine, N-acetylglutamic acid, N-acetylproline,N-acetylhydroxyproline, lactic acid, malic acid and citric acid andalkali metal salts thereof, pyrrolidonecarboxylic acids,alkylpyrrolidonecarboxylic acid esters, N-alkylpyrrolidones, prolineacyl esters, sodium lauryl phosphate, sodium lauryl sulphate, sodiumoleyl phosphate, sodium myristyl sulphate, polyoxyethylene alkyl ethers,polyoxyethylene alkyl esters, and caproic acid, alkylsaccharide, fusidicacid, polyethylene glycol, cetyl alcohol, polyvinylpyrolidone, Polyvinylalcohol, Lanolin alcohol, Sorbitan monooleate, Ethylene glycoltetraacetic acid, Bile acid conjugate with taurine, Cholanic acid andsalts, Cyclodextran, Cyclodextrin, Cyclodextrin (beta),Hydroxypropyl-β-cyclodetran, Sulfobutylether-β-cyclodextran,Methyl-β-cyclodextrin, Chitosan glutamate, Chitosan acetate, Chitosanhydrochloride, Chitosan hydrolactate,1-O-alkyl-2-hydroxy-sn-glycero-3-phosphocholine,3-O-alkyl-2-acetoyl-sn-glycero-1-phosphocholine,1-O-alkyl-2-O-acetyl-sn-glycero-3-phospho(N,N,N-trimethyl)hexanolamine,Propylene glycol, Tetradecylmaltoside (TDM), Sucrose dedecanoate.

According to an embodiment of the invention, the enhancer comprises oneor more pH control agent, such as a buffering agent.

In an embodiment of the invention, said pH control agents are selectedfrom the group consisting of Acetic acid, Adipic acid, Citric acid,Fumaric acid, Glucono-δ-lactone, Gluconic acid, Lactic acid, Malic acid,Maleic acid, Tartaric acid, Succinic acid, Propionic acid, Ascorbicacid, Phosphoric acid, Sodium orthophosphate, Potassium orthophosphate,Calcium orthophosphate, Sodium diphosphate, Potassium diphosphate,Calcium diphosphate, Pentasodium triphosphate, Pentapotassiumtriphosphate, Sodium polyphosphate, Potassium polyphosphate, Carbonicacid, Sodium carbonate, Sodium bicarbonate, Potassium carbonate, Calciumcarbonate, Magnesium carbonate, Magnesium oxide, or any combinationthereof.

According to an embodiment of the invention, the water-insolublecomposition comprises cellulose, e.g. as a carrier.

In an embodiment of the invention the cellulose is or comprisesmicrocrystalline cellulose.

One advantage of the above embodiment may be that microcrystallinecellulose may absorb a relatively high amount of cannabinoid, while alsoallowing for the one or more cannabinoids to be effectively releasedfrom the pouch during use.

The cellulose may be synthetic or semisynthetic celluloses, or it may bederived from natural celluloses. It is normally crystalline such asmicrocrystalline. Certain specific embodiments may also utilize otherforms of carriers, in addition to or including mcc, such as but notlimited to fibrous material or carbohydrates including cellulose(including hemicellulose, celluloses with different crystallinities andstructures (e.g. varying structures including solid fibers, and additionor including fibers or the like in various structures such as web-likestructures and/or other structures), including naturally occurringcelluloses including Cladophora sp. Algae cellulose or the like),dextran, agarose, agar, pectin, alginate, xanthan, chitosan, starch(including potato starch, shoti starch) etc. or mixtures thereof.

The microcrystalline cellulose may be selected from the group consistingof AVICEL® grades PH-100, PH-102, PH-103, PH-105, PH-112, PH-113,PH-200, PH-300, PH-302, VIVACEL® grades 101, 102, 12, 20 and EMOCEL®grades 50M and 90M, and the like, and mixtures thereof.

In an embodiment of the invention said cellulose is provided in the formof particles having an average particle size between 1 and 1000micrometers, such as between 10 and 250 micrometers, such as between 15and 200 micrometers, such as between 20 and 150 micrometers, such asbetween 50 and 100 micrometers, such as about 75 micrometers.

In an embodiment of the invention said cellulose has a specific surfacearea of between 0.65 and 1.5 m²/g, such as between 0.75 and 1.25 m²/g,such as between 0.85 and 1.15 m²/g, such as between 0.9 and 1.1 m²/g,such as about 0.95 m²/g, about 1.00 m²/g, or such as about 1.05 m²/g.

In an embodiment of the invention said cellulose has a bulk densitybetween 0.1 and 1.0 grams per cubic centimeter (g/cm³), such as between0.25 and 0.5 grams per cubic centimeter, such as between 0.26 and 0.31grams per cubic centimeter, or such as between 0.28 and 0.33 grams percubic centimeter.

In the context of the above embodiment it should preferably beunderstood that the bulk density of the cellulose is understood as thebulk density at about 25 degrees Celsius.

In an embodiment of the invention said cellulose has a porositycharacterized by an average specific pore volume between 0.003 cm³/g and0.60 cm³/g, such as between 0.01 and 0.3 cm³/g.

In an embodiment of the invention said cellulose has a moisture contentof less than about 5% by weight, such as between 2 and 5% by weight,such as between 3 and 5% by weight, such as about 4% by weight.

Various types of usable cellulose includes microcrystalline cellulose(MCC); carboxymethylcellulose (CMC), such as sodiumcarboxymethylcellulose; hydroxypropyl methylcellulose (HPMC);methylcellulose; ethylcellulose (EC); methylethylcellulose (MEC);hydroxyethyl cellulose (HEC); hydroxyethyl methylcellulose (HEMC); andany combination thereof.

In an embodiment of the invention said cellulose has an average fibersize of less than 200 micrometers, such as between 75 and 125micrometers, or such as below 75 micrometers.

In an embodiment of the invention the cellulose comprises pores, thepores having an average pore size of between about 3 nanometers andabout 300 nanometers, such as between 10 nanometers and 200 nanometers,such as between 20 nanometers and 100 nanometers.

In an embodiment of the invention said cellulose is derived from naturalsources, such as wood pulp.

Other examples of natural sources of cellulose include sugar beet fiber,cotton fiber, bran fiber, citrus pulp fiber, grass fiber, willow fiber,poplar fiber, bamboo fiber, and combinations thereof, or combinationsthereof with wood pulp.

In some embodiments, the cellulose can be chemically treated, e.g. bymeans of CMC, MPMC, HPC, MCC, and/or other methods.

Alternatively, the cellulose may be semi-synthetic or syntheticcellulose.

According to an embodiment of the invention the water-insolublecomposition comprises an ion-exchange resin, such as a basicion-exchange resin, e.g. a strongly basic ion-exchange resin.

The ion-exchange resin, such as the basic ion-exchange resin, of thewater-insoluble composition may be part of the carrier when the matrixcomposition comprises a carrier.

The one or more cannabinoids may, especially when using a basicion-exchange resin, be selected from the cannabinoids having at leastone phenolic moiety. By using cannabinoid(s) having at least onephenolic moiety, the basic group of the basic ion exchange resin has oneor more groups on the cannabinoid(s) to bind with. The cannabinoid(s)may in some embodiment optionally comprise one or more carboxylicgroups, thus adding to the potential binding sites for the basic ionexchange resin.

In an embodiment of the invention the ion exchange resin(s) acts as astabilization agent.

One very important advantage of the above embodiment may be that theamount of cannabinoid(s) available for body uptake is advantageouslypreserved due to the stabilization of the cannabinoid(s).

In an advantageous embodiment of the invention the basic ion exchangeresin comprises strongly basic ion exchange resin.

One advantage of the above embodiment may be that a relatively effectivestabilization of the cannabinoid(s) may be achieved, while synchronizedrelease of the cannabinoid(s) from the complex, i.e. synchronized withthe intended time of delivery to the body may be achieved, e.g. in oneembodiment by adding an acid to the pouch.

In an advantageous embodiment of the invention the basic ion exchangeresin is strongly basic ion exchange resin.

One advantage of the above embodiment may be that a relatively effectivestabilization of the cannabinoid(s) may be achieved, while synchronizedrelease of the cannabinoid(s) from the complex, i.e. synchronized withthe intended time of delivery to the body may be achieved, e.g. in oneembodiment by adding an acid to the pouch.

In an advantageous embodiment of the invention the basic ion exchangeresin comprises weakly basic ion exchange resin.

One advantage of the above embodiment may be that a relatively effectiverelease of the cannabinoid(s) from the complex may be obtained, in someembodiments without using any agents, such as acids, for facilitatingrelease of the cannabinoid(s) from the complex.

In an advantageous embodiment of the invention said basic ion exchangeresin is a strongly basic ion exchange resin comprising one or morequaternary amino groups.

Examples of strongly basic ion exchange resins include for examplecommercially available products, such as Ambersep® 900, Cholestyramine,and Duolite AP143.

In an advantageous embodiment of the invention the basic ion exchangeresin are selected from the group consisting of Ambersep 900,Cholestyramine, Duolite AP143, Amberlite CG-400, Amberlite IRA-400,Amberlite IRA-401, Amberlite IRA-410, Amberlite IRA-900, and AmberliteIRA-904.

In an advantageous embodiment of the invention the basic ion exchangeresin comprises cross-linked polystyrene.

In an advantageous embodiment of the invention the basic ion exchangeresin comprises cross-linked polystyrene, wherein the cross-linkingagent comprises or is divinylbenzene.

In an advantageous embodiment of the invention the basic ion exchangeresin comprises a styrene-divinylbenzene copolymer.

According to an embodiment of the invention, the basic ion exchangeresin is a styrene-divinylbenzene copolymer functionalized by basicgroups, such as amine groups. If a strongly basic ion exchange resin isdesirable, strongly basic functional groups, such as quaternary amines,are used; whereas if a weakly basic ion exchange resin is desirable,weakly basic functional groups, such a primary, secondary, or tertiaryamine groups, are used.

In an advantageous embodiment of the invention the basic ion exchangeresin has a counter ion selected from the group consisting of hydroxide,chloride, and bromide, before reaction with the one or morecannabinoids.

According to various embodiments of the invention, sugar alcohols may beincluded in the pouch as a matrix composition or part thereof as ahumectant, or as a sweetener. Suitable sugar alcohols include sugaralcohols selected from the group of sorbitol, erythritol, xylitol,lactitol, maltitol, mannitol, hydrogenated starch hydrolyzates, isomalt,or any combination thereof.

In an embodiment of the invention the pouch comprises high intensitysweetener.

Preferred high intensity sweeteners include, but are not limited tosucralose, aspartame, salts of acesulfame, such as acesulfame potassium,alitame, saccharin and its salts, cyclamic acid and its salts,glycyrrhizin, dihydrochalcones, thaumatin, monellin, stevioside and thelike, alone or in combination.

In an embodiment of the invention, the pouch comprises bulk sweetenersincluding sugar and/or sugarless components.

In an embodiment of the invention, the pouch comprises bulk sweetener inthe amount of 5 to about 95% by weight of the pouch, more typicallyconstitute 20 to about 80% by weight of the pouch, and more commonly, 30to 60% by weight of the pouch. Bulk sweeteners may function both as asweetener and also as a humectant.

The sweeteners may often support the flavor profile of the pouch.

Sugar sweeteners generally include, but are not limited tosaccharide-containing components commonly known in the art of pouches,such as sucrose, dextrose, maltose, saccharose, lactose, sorbose,dextrin, trehalose, D-tagatose, dried invert sugar, fructose, levulose,galactose, corn syrup solids, glucose syrup, hydrogenated glucose syrup,and the like, alone or in combination. These sugar sweeteners may alsobe included as a humectant.

The sweetener can be used in combination with sugarless sweeteners.Generally, sugarless sweeteners include components with sweeteningcharacteristics but which are devoid of the commonly known sugars andcomprise, but are not limited to, sugar alcohols, such as sorbitol,mannitol, xylitol, hydrogenated starch hydrolyzates, maltitol, isomalt,erythritol, lactitol and the like, alone or in combination. Thesesugarless sweeteners may also be included as a humectant.

In an embodiment of the invention the pouch comprises flavor. Flavor maytypically be present in amounts between 0.01 and 10% by weight of thetotal composition of the pouch, such as between 0.01 and 5% by weight ofthe total composition.

Non-exhaustive examples of flavors suitable in embodiments of thepresent invention are coconut, coffee, chocolate, vanilla, grape fruit,orange, lime, menthol, liquorice, caramel aroma, honey aroma, peanut,walnut, cashew, hazelnut, almonds, pineapple, strawberry, raspberry,tropical fruits, cherries, cinnamon, peppermint, wintergreen, spearmint,eucalyptus, and mint, fruit essence such as from apple, pear, peach,strawberry, apricot, raspberry, cherry, pineapple, and plum essence. Theessential oils include peppermint, spearmint, menthol, eucalyptus, cloveoil, bay oil, anise, thyme, cedar leaf oil, nutmeg, and oils of thefruits mentioned above.

In various embodiments of the invention, the matrix compositioncomprises a release controlling composition for controlling the releaseof the matrix composition and/or parts thereof, especially the one ormore cannabinoids.

The release controlling composition may, according to variousembodiments, be selected group consisting of metallic stearates,modified calcium carbonate, hydrogenated vegetable oils, partiallyhydrogenated vegetable oils, polyethylene glycols, polyoxyethylenemonostearates, animal fats, silicates, silicates dioxide, talc,magnesium stearates, calcium stearates, fumed silica, powderedhydrogenated cottonseed oils, hydrogenated vegetable oils, hydrogenatedsoya oil and mixtures thereof. Particularly, metallic stearates, such asmagnesium stearate may be advantageous.

According to an embodiment of the invention said modified calciumcarbonate is made according to US patent application US 2012/0039981 A1,hereby incorporated by reference, particularly as in the examplestherein.

The release controlling composition may be added to the matrixcomposition in various ways.

For example, the release controlling composition may be added by fullpowder mixture during the last few minutes of the final mixing.

Alternatively, the release controlling composition may be added afterthe granulation steps on a granulation premix.

Still further, the release controlling composition may be added only asa fraction of the matrix composition so two different release profilesof cannabinoids are achieved. Even further two or more fractions of thematrix composition may comprise different amounts of the releasecontrolling composition, if any, thereby providing a more complex andtailored release profile of cannabinoids.

The release controlling composition, such as magnesium stearate, mayhave a sealing effect and can be used to control the release of the oneor more cannabinoids and the solubility of the matrix composition.

According to an embodiment of the invention, the pouch comprisespolyvinylpyrrolidone (PVP).

One advantage of the above embodiment may be that a more uniformcomposition may be obtained.

EXAMPLES

The following examples are illustrative of the present invention andshould not be considered as limiting the scope of the invention.

Examples 1-3 illustrate various raw materials and methods for preparingintermediate ingredients.

Examples 4-8 discloses a number of different pouches and theirrespective compositions.

Example 1

Preparation of Cannabinoid Powder Composition

Cannabinoids come in different grades and form from pasta, oil andcrystals and in different concentrations. Depending on the form ofcannabinoids the manufacturing steps will vary.

As illustrated in the following examples, cannabinoids can be added aspowder or sorbed, mixed or granulated on different carriers asmicrocrystalline cellulose (MCC) or sugar alcohols etc.

Example 2

Preparation of Pouches Designed for Administration of Cannabinoids

The material of the pouches is heat sealable non-wowen cellulose.

The powder is filled into pouches and is maintained in the pouch by asealing.

Example 3

Preparation of Pouches with Water-Insoluble Composition

Cannabinoids used in example 3 are obtained in accordance with example1, The pouches described in example 2 are used.

Herein, target fill weight 400 mg powder per pouch. Alternatively,target fill weights of e.g. 250 mg or 800 mg could be used.

Example 3.1

The cannabinoids are dissolved in ethanol with a weight ratio of about1:1 to form a homogeneous granulation solution. The granulation solutionis slowly added to the microcrystalline cellulose under stirring(Kitchenaid mixer operated at about 30 RPM in about 30 minutes). Theresulting granulate is sieved and placed on a tray. The resulting powderis dried at ambient temperature overnight and is thereafter sieved.

A fine-grained powder of cannabinoids-microcrystalline cellulose carriercomplex was obtained.

The obtained cannabinoids-microcrystalline cellulose carrier complex ismixed with the remaining ingredients to obtain a final powdercomposition.

The final powder composition is manually filled into pouches (targetfill weight 400 mg powder per pouch). The pouch of example 2, made fromlong fiber paper, is used.

Magnesium stearate, if any, is added by full powder mixture during thelast few minutes of the final mixing. When including smaller amounts offurther humectants, apart from e.g. MCC and/or sugar alcohols, thesefurther humectants are added in the same manner as magnesium stearate.

Example 3.2

The cannabinoids are dissolved in ethanol with a weight ratio of about1:1 and the Kollidon 25 (polyvinylpyrrolidone) is added together withthe liquid flavor to form a homogeneous granulation solution.

The following solid components are mixed and sieved to form a powdermixture: mannitol, MCC, high intensive sweetener and flavors.

The granulation solution is slowly added to the powder mixture understirring (Kitchenaid mixer operated at about 30 RPM in about 30minutes). The resulting granulate is sieved and placed on a tray. Theresulting powder is dried at ambient temperature overnight and isthereafter sieved to obtain a final powder composition.

The final powder composition is manually filled into pouches (targetfill weight 400 mg powder per pouch). The pouch of example 2, made fromlong fiber paper, is used.

Magnesium stearate, if any, is added by full powder mixture during thelast few minutes of the final mixing. When including smaller amounts offurther humectants, apart from e.g. MCC and/or sugar alcohols, thesefurther humectants are added in the same manner as magnesium stearate.

Example 3.3

The ion exchange resin complex is made by dissolving the cannabinoids(882 g CBD) in 88 L ethanol to form a homogeneous solution, NaOH can beadded to make the binding of the cannabinoid(s) and the ion-exchangeresin better.

5 kg of ion exchange resin (Ambersep 900 on OH-form) is added. When allthe CBD solution has been bound by the ion exchange resin the pressureis reduced and the obtained mixture is concentrated in vacuo at elevatedtemperature affording the desired complex as a powder.

The obtained powder is mixed with the remaining ingredients to obtain afinal powder composition. An acid like citric acid can be added toincrease the release of the cannabinoid(s) from the resin during usage.

The final powder composition is manually filled into pouches (targetfill weight 400 mg powder per pouch). The pouch of example 2, made fromlong fiber paper, is used.

Magnesium stearate, if any, is added by full powder mixture during thelast few minutes of the final mixing. When including smaller amounts offurther humectants, apart from e.g. sugar alcohols, these furtherhumectants are added in the same manner as magnesium stearate.

Glycerin may also be added, for example in amounts giving a ratio ofglycerin to ion exchange resin of about 1 to 3.4.

Example 3.4

A powder composition obtained the same way as the final powdercompetition in example 3.3. Thereafter, polyvinylpyrrolidone (Kollidon25) is added to form a granulation solution. The resulting granulate issieved and placed on a tray. The resulting powder is dried at ambienttemperature overnight and is thereafter sieved to obtain a final powdercomposition.

The final powder composition manually filled into pouches (target fillweight 400 mg powder per pouch). The pouch of example 2, made from longfiber paper, is used.

Magnesium stearate, if any, is added by full powder mixture during thelast few minutes of the final mixing. When including smaller amounts offurther humectants, apart from e.g. sugar alcohols, these furtherhumectants are added in the same manner as magnesium stearate.

Example 4

Preparation of Pouches with Water-Insoluble Composition

TABLE 1 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 101 102103 104 105 106 107 Method cf. example 3.1 3.1 3.2 3.3 3.3 3.4  3.4**Raw material Content in weight percent CBD extract 5.00* 5.00* 5.00*5.00* 5.00* 5.00*  5.00* NaOH — — — — — — 0.60 Citric acid — — — — — —0.70 Mannitol 43.45 73.45 65.45 43.45 73.45 65.45 64.15  MCC 50.00 20.0020.00 — — — — Ion exchange resin — — — 50.00 20.00 20.00 20.00  Flavor1.50 1.50 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.05 0.05 0.05 0.05 0.050.05 PVP — — 8.00 — — 8.00 8.00 Total 100 100 100 100 100 100 100    *5%CBD corresponds to 10 mg CBD/pouch. Pouches contain 400 mg per piece.MCC is microcrystalline cellulose. Ion exchange resin is an Ambersep 900on OH-form. HIS = High intense sweetener may for example be sucralose.Flavor may for example be pepper mint flavor. PVP =polyvinylpyrrolidone, Kollidon 25.

As shown in table 1, different water-insoluble compositions may be used,including MCC and ion-exchange resin, and in different amounts. Possibleinclusion of PVP is also shown, as well as inclusion of base (here NaOH)and acid (here citric acid) when using ion exchange resin.

Example 5

Preparation of Pouched with Magnesium Stearate

TABLE 2 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 108 109110 Method cf. example 3.1 3.3 3.4 Raw material Content in weightpercent CBD extract 5.00* 5.00* 5.00* Mannitol 63.45 63.45 55.45 MCC20.00 — — Ion exchange resin — 20.00 20.00 Flavor 1.50 1.50 1.50 HIS0.05 0.05 0.05 PVP — — 8.00 MgSt 10.00 10.00 10.00 Total 100 100 100 *5%CBD corresponds to 10 mg CBD/pouch. Pouches contain 400 mg per piece.MCC is microcrystalline cellulose. Ion exchange resin is an Ambersep 900on OH— form. HIS = High intense sweetener may for example be sucralose.Flavor may for example be peppermint flavor. PVP = polyvinylpyrrolidone,Koliidon 25. MgSt is magnesium stearate and is added as a releasecontrolling composition.

As shown in table 2, magnesium stearate (MgSt) can be included in thepouch in combination with both MCC and ion exchange resin. Magnesiumstearate has a sealing effect and can be used to control the release ofCBD and the solubility of the matrix composition. PVP may also beincluded.

Example 6

Preparation of Pouched with Different Cannabinoids and DifferentPurifications

TABLE 3 Cannabinoid pouch; CBD used corresponds to 10 mg CBD/pouch.Pouch no. 111 112 113 114 115 Method cf. example 3.1 3.1 3.1 3.1 3.1 Rawmaterial Content in weight percent CBD pure (99.5%) 2.51 — — — 2.51 CDBextract (50%) — 5.00 — — — CDB extract (10%) — — 25.00 — — THC pure(99.5%) — — — 2.51 2.51 Mannitol 75.94 73.45 53.45 75.94 68.43 MCC 20.0020.00 20.00 20.00 20.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.050.05 0.05 0.05 MgSt — — — — 5 Total 100 100 100 100 100 THC usedcorresponds to 10 mg THC/pouch. Pouches contain 400 mg per piece. MCC ismicrocrystalline cellulose. HIS = High intense sweetener may for examplebe sucralose. Flavor may for example be pepper mint flavor. MgSt ismagnesium stearate and is added as a releasing agent.

As shown in table 3, different cannabinoids, CBD and THC, may be used.Also, different concentrations of the cannabinoids may be used, hereillustrated as 10% extract, 50% extract, or 99.5% pure cannabinoids.Finally, different cannabinoids may be combined, here shown by acombination of CBD and THC.

Example 7

Preparation of Pouches with Different Concentrations of Cannabinoidswhen Using Pure CBD (99.5%):

TABLE 4 Cannabinoid pouch; CBD is used in different dosage from 5-100 mgCBD/pouch - CBD extract of 99.5% has been used. Pouch no. 116 117 118119 120 Method cf. example 3.2 3.2 3.2 3.2 3.2 Amount of cannabinoids 5mg 10 mg 20 mg 50 mg 100 mg Raw material Content in weight percent CDB1.26 2.51 5.03 12.56 25.13 Isomalt 64.19 62.94 60.42 42.89 30.32 MCC20.00 20.00 20.00 30.00 30.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.050.05 0.05 0.05 0.05 PVP 8.00 8.00 8.00 8.00 8.00 MgSt 5.00 5.00 5.005.00 5.00 Total 100 100 100 100 100 Pouches contain 400 mg per piece.MCC is microcrystalline cellulose. HIS = High intense sweetener may forexample be sucralose. Flavor may for example be pepper mint flavor. MgStis magnesium stearate and is added as a releasing agent. PVP =polyvinylpyrrolidone, Kollidon 25. CBD could be replaced with THC or bein combination with THC.When Using CBD (50% Pure):

TABLE 5 Cannabinoid pouch; CBD is used in different dosage from 5-100 mgCBD/pouch - CBD extract of 50% has been used. Pouch no. 121 122 123 124125 Method cf. example 3.2 3.2 3.2 3.2 3.2 Amount of cannabinoids 5 mg10 mg 20 mg 50 mg 100 mg Raw material Content in weight percent CDB 2.505.00 10.00 25.00 50.00 Isomalt 62.95 60.45 55.45 30.45 5.45 MCC 20.0020.00 20.00 30.00 30.00 Flavor 1.50 1.50 1.50 1.50 1.50 HIS 0.05 0.050.05 0.05 0.05 PVP 8.00 8.00 8.00 8.00 8.00 MgSt 5.00 5.00 5.00 5.005.00 Total 100 100 100 100 100 Pouches contain 400 mg per piece. MCC ismicrocrystalline cellulose. HIS = High intense sweetener may for examplebe sucralose. Flavor may for example be pepper mint flavor. MgSt ismagnesium stearate and is added as a releasing agent. PVP =polyvinylpyrrolidone, Kollidon 25. CBD could be replaced with THC or bein combination with THC.

As shown in tables 4-5, different total amounts of cannabinoids (hereCBD) may be used in the pouch, regardless of using relatively purecannabinoids or if using an extract comprising other components.

Example 8

Preparation of Pouches with Different Humectants

TABLE 6 Cannabinoid pouch; CBD used is a 50% extract. Pouch no. 126 127128 129 Method cf. example 3.1 3.1 3.1 3.1 Raw material Content inweight percent CBD extract 5.00* 5.00* 5.00* 5.00* Isomalt 73.45 71.4571.45 71.45 MCC 20.0 20.0 20.0 20.0 Flavor 1.50 1.50 1.50 1.50 HIS 0.050.05 0.05 0.05 Glycerol — 2.00 — — Sodium alginate — — 2.00 — Pectin — —— 2.00 Total 100 100 100 100 *5% CBD corresponds to 10 mg CBD/pouch.Pouches contain 400 mg per piece. MCC is microcrystalline cellulose. HIS= High intense sweetener may for example be sucralose. Flavor may forexample be pepper mint flavor. Glycerol, sodium alginate and pectin areaction as moistening or lubricant agent.

As shown in table 6, different further humectants may be added.Humectants attract the saliva from the mouth and make sure that water isavailable in the pouch. Increased water increase the release.

Example 9

Evaluation

The pouches produced were evaluated and found highly suitable asdelivery vehicles for cannabinoids.

The invention claimed is:
 1. A pouch designed for administration of anactive ingredient in the oral cavity, the pouch containing a matrixcomposition comprising: powdered granules comprising a combination of anamount of one or more cannabinoids; and a water-insoluble compositioncomprising microcrystalline cellulose (MCC), wherein the matrixcomposition further comprises a water-soluble composition comprising oneor more sugar alcohols, and wherein the pouch comprises awater-permeable membrane.
 2. The pouch according to claim 1, wherein thematrix composition comprises said water-insoluble composition in anamount of between 1 and 80 percent by weight of said matrix composition.3. The pouch according to claim 1, wherein the water-insolublecomposition further comprises an ion-exchange resin.
 4. The pouchaccording to claim 3, wherein the ion-exchange resin is present in anamount of 5 to 60 percent of said matrix composition.
 5. The pouchaccording to claim 1, wherein the matrix composition further comprises arelease controlling composition.
 6. The pouch according to claim 5,wherein said release controlling composition is hydrophobic.
 7. Thepouch according to claim 5 wherein said release controlling compositioncomprises one or more metallic stearates.
 8. The pouch according toclaim 5, wherein the matrix composition comprises said releasecontrolling composition in an amount of between 1 and 20 percent byweight of said matrix composition.
 9. The pouch according to claim 1,wherein the one or more cannabinoids is physically or chemically boundto at least a part of the matrix composition acting as a carrier. 10.The pouch according to claim 1, wherein the one or more cannabinoidscomprises cannabidiol.
 11. The pouch according to claim 1, wherein theone or more cannabinoids comprises tetrahydrocannabinol.
 12. The pouchaccording to claim 1, wherein the pouch further comprises a humectant.13. A pouch designed for administration of an active ingredient in theoral cavity, the pouch containing a matrix composition comprising: apowder composition comprising an amount of one or more cannabinoids; awater-soluble composition comprising one or more sugar alcohols; and awater-insoluble composition comprising microcrystalline cellulose (MCC),wherein the pouch comprises a water-permeable membrane.
 14. A pouchdesigned for administration of an active ingredient in the oral cavity,the pouch containing a powdered matrix composition comprising: an amountof one or more cannabinoids; a water-soluble composition comprising oneor more sugar alcohols; and a water-insoluble composition comprisingmicrocrystalline cellulose (MCC), wherein the one or more cannabinoidsis physically or chemically bound to at least a part of the powderedmatrix composition acting as a carrier, and wherein the pouch comprisesa water-permeable membrane.
 15. The pouch according to claim 13, whereinthe water-permeable membrane is a woven fabric.
 16. The pouch accordingto claim 13, wherein the water-permeable membrane is a non-woven fabric.17. The pouch according to claim 13, wherein the matrix compositioncomprises said one or more cannabinoids in an amount of 0.25 to 500milligrams.
 18. The pouch according to claim 13, wherein the one or morecannabinoids is physically or chemically bound to at least a part of thematrix composition acting as a carrier.
 19. The pouch according to claim13, wherein the matrix composition comprises said water-insolublecomposition in an amount of between 1 and 80 percent by weight of saidmatrix composition.
 20. The pouch according to claim 14, wherein the oneor more cannabinoids comprises cannabidiol and/or tetrahydrocannabinol.21. The pouch according to claim 14, wherein the pouch further comprisesa humectant.
 22. The pouch according to claim 14, wherein the powderedmatrix composition has an average particle size between 1 and 1200micrometers.